Discovery and structure-activity relationships of phenyl benzenesulfonylhydrazides as novel indoleamine 2,3-dioxygenase inhibitors
Discovery and structure-activity relationships of phenyl benzenesulfonylhydrazides as novel indoleamine 2,3-dioxygenase inhibitors
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DOI：
10.1016/j.bmcl.2014.05.084
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发表时间：
2014-08-01
影响因子：
2.7
通讯作者：
Ueng, Shau-Hua
中科院分区：
文献类型：
--
作者：
Cheng, Ming-Fu;Hung, Ming-Shiu;Ueng, Shau-Hua
一类新型苯磺酰肼已被鉴定为吲哚胺 2,3-双加氧酶 (IDO) 的有效抑制剂，并探讨了它们的结构-活性关系。利用各种苯磺酰氯与苯酰肼之间的偶联反应合成带有各种取代基的磺酰肼。化合物 3i 在酶测定中表现出 61 nM 的 IC50 ，在 HeLa 细胞中表现出 172 nM EC50 。 3i的计算研究表明3i和IDO蛋白之间的主要相互作用是砜和血红素铁的配位、3i和IDO之间的氢键和疏水相互作用。这类新型IDO抑制剂为发现有效的抗癌药物提供了新的方向。 (C) 2014 Elsevier Ltd. 保留所有权利。
A novel class of phenyl benzenesulfonylhydrazides has been identified as potent inhibitors of indoleamine 2,3-dioxygenase (IDO), and their structure-activity relationship was explored. Coupling reactions between various benzenesulfonyl chlorides and phenylhydrazides were utilized to synthesize the sulfonylhydrazides bearing various substituents. Compound 3i exhibited 61 nM of IC50 in enzymatic assay and 172 nM of EC50 in the HeLa cell. The computational study of 3i suggested that the major interactions between 3i and IDO protein are the coordination of sulfone and heme iron, the hydrogen bonding and hydrophobic interactions between 3i and IDO. This novel class of IDO inhibitor provides a new direction to discover effective anti-cancer agents. (C) 2014 Elsevier Ltd. All rights reserved.